Metabolism of glutathione and a glutathione conjugate by isolated kidney cells.
Metabolism of glutathione and a glutathione conjugate by isolated kidney cells.
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分离的肾细胞对谷胱甘肽和谷胱甘肽缀合物的代谢。
DOI：
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发表时间：
1979
影响因子：
4.8
通讯作者：
S. Orrenius
中科院分区：
文献类型：
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作者：
D. P. Jones;P. Moldfus;A. Stead;K. Ormstad;H. Jörnvall;S. Orrenius
在离体大鼠肾上皮细胞悬液中研究了外源性谷胱甘肽和谷胱甘肽结合物的代谢。1.谷胱甘肽（GSH）被肾细胞悬液迅速氧化为谷胱甘肽二硫化物（GSSG）。该反应被KCN抑制，并依赖于O2和GSH浓度。添加丝氨酸硼酸盐，一种特异性的γ-谷氨酰转移酶抑制剂，对GSH损失率没有影响。这些结果表明，外源性GSH在肾脏代谢的第一步是氧化成GSSG。2.在GSH或GSSG代谢过程中形成的中间肽与作为起始底物的GSH或GSSG相同。对中间体蓄积速率的分析表明，GSSG代谢过程中的第一个反应是去除1-γ谷氨酰残基。然后发生来自相同GSH部分的甘氨酰残基的水解以形成GSH和半胱氨酸的混合二硫化物，并且这之后是第二个γ-谷氨酰残基的去除。最后，除去第二个甘氨酰残基。胱氨酸的摩尔回收率相当于加入的初始GSSG，谷氨酸和甘氨酸的积累对应于中间肽的形成。添加丝氨酸l
The metabolism of exogenously added glutathione and a glutathione conjugate was studied in suspensions of isolated rat kidney epithelial cells. 1. Glutathione (GSH) was oxidized rapidly to glutathione disulfide (GSSG) by kidney cell suspensions. The reaction was inhibited by KCN and was dependent upon both O2 and GSH concentrations. Addition of serine l borate, a specific inhibitor of y-glutamyltransferase, had no effect on the rate of GSH loss. These results suggest that an initial step in metabolism of exogenous GSH in kidney is an oxidation to GSSG. 2. Intermediate peptides formed during GSH or GSSG metabolism were the same with either GSH or GSSG as the starting substrate. Analysis of the rates of accumulation of the intermediates suggested that the first reaction during metabolism of GSSG is removal of 1 yglutamyl residue. Hydrolysis of the glycyl residue from the same GSH moiety then occurs to form the mixed disulfide of GSH and cysteine, and this is followed by removal of the 2nd y-glutamyl residue. Finally, the 2nd glycyl residue is removed. The molar recovery of cystine was equivalent to the initial GSSG added and glutamate and glycine accumulation corresponded to formation of intermediate peptides. Addition of serine l